evaluation of [18f]alf-nota-pcp2 pet/ct for pd-l1 detection in malignant tumors

Conditions: Glioblastoma (GBM); Head and Neck Squamous Cell Carcinoma; Non-Small Cell Lung Cancer; Esophageal Cancer

Summary: this phase i/ii clinical trial evaluates the safety, efficacy, and prognostic potential of \[18f\]alf-nota-pcp2 pet/ct imaging in assessing pd-l1 expression in malignant tumors, including glioblastoma, head and neck squamous cell carcinoma, non-small cell lung cancer, and esophageal cancer. the primary aim is to establish the correlation between \[18f\]alf-nota-pcp2 uptake and pd-l1 expression in tumor tissues, while secondary objectives include evaluating its role in predicting clinical outcomes such as progression-free survival (pfs) and overall survival (os). by providing a non-invasive, quantitative, and reproducible method for assessing pd-l1, this study aims to refine patient stratification and improve the precision of immunotherapy decision-making.

this phase i/ii clinical trial is designed to explore the utility of \[18f\]alf-nota-pcp2 pet/ct in evaluating pd-l1 expression and its prognostic implications in patients with malignant tumors (glioblastoma, head and neck squamous cell carcinoma, non-small cell lung cancer, and esophageal cancer). the study involves at least 20 patients (5 per tumor type) who will undergo a pre-treatment pet/ct scan following an intravenous injection of \[18f\]alf-nota-pcp2. the primary endpoints include the safety of the imaging protocol and the correlation between \[18f\]alf-nota-pcp2 uptake (suv values) and pd-l1 expression determined through immunohistochemistry (ihc). secondary endpoints explore the dynamic changes in suv values in patients undergoing multiple scans and their relationship with clinical outcomes. scientific and technical rationale: \[18f\]alf-nota-pcp2 is a novel radiotracer with high specificity for pd-l1, enabling non-invasive imaging of its expression in vivo. this imaging approach complements traditional immunohistochemical methods by offering whole-body assessment, eliminating the need for repeated biopsies, and providing insights into the tumor microenvironment. this study seeks to validate its application in clinical oncology, bridging molecular imaging with biomarker-guided therapeutic strategies. study methods: patients will receive a single intravenous dose of \[18f\]alf-nota-pcp2 (adjusted for body weight), followed by a whole-body pet/ct scan after one hour. images will be analyzed independently by two experienced nuclear medicine specialists. tumor biopsies will be collected to measure pd-l1 expression via ihc, and blood samples will be assessed for circulating and exosomal pd-l1 biomarkers. for patients undergoing multiple scans, changes in radiotracer uptake will be tracked to monitor treatment response. data analysis: suv values will be correlated with pd-l1 expression levels, clinical factors (e.g., tumor stage, histology), and patient outcomes (pfs, os). statistical analyses, performed using spss 29.0, will include primary correlations and secondary evaluations of imaging-based dynamic changes and their relationship with therapeutic efficacy. significance: this trial will provide critical data on the feasibility of \[18f\]alf-nota-pcp2 pet/ct imaging in clinical oncology. its potential to stratify patients based on pd-l1 expression and predict therapy response could transform personalized cancer care, optimizing immunotherapy outcomes and minimizing unnecessary treatments. timeline: patient enrollment is expected to last 12 months, with an additional 3 months of follow-up for data collection and analysis.

Eligibility criteria:
inclusion criteria: * signed informed consent obtained. * age ≥ 18 years, any gender. * pathologically confirmed malignant tumors, including: * glioblastoma * head and neck squamous cell carcinoma * non-small cell lung cancer * esophageal cancer * detectable pd-l1 expression in tumor tissue (based on immunohistochemistry or biopsy). * measurable disease with at least one residual tumor lesion. * ecog performance status of 0-1. * no contraindications to \[18f\]alf-nota-pcp2 pet/ct imaging. * willing and able to comply with study procedures and follow-up visits. exclusion criteria: * participation in another interventional clinical trial. * failure to recover from toxic effects or complications of prior interventions (≤ grade 1 or baseline levels, excluding fatigue or hair loss). * pregnant or breastfeeding women. * severe or uncontrolled systemic diseases, including: * major, symptomatic arrhythmias or significant ecg abnormalities (e.g., complete left bundle branch block, second-degree or higher heart block, or ventricular arrhythmias). * unstable angina or congestive heart failure (nyha class ≥ 2). * any arterial thrombotic or embolic events within 6 months before enrollment (e.g., myocardial infarction, cerebrovascular accident, transient ischemic attack). * active or uncontrolled infections requiring systemic treatment. * severe psychiatric disorders affecting study participation. * any medical history, laboratory abnormality, or condition that may: * interfere with study results. * affect patient participation. * pose an unacceptable risk as determined by the investigator. * women of childbearing potential without a negative pregnancy test prior to study entry. * known allergy or hypersensitivity to \[18f\]alf-nota-pcp2 or any component of the radiopharmaceutical.

Keywords: pet/ct pd-l1 expression [18f]alf-nota-pcp2 glioblastoma head and neck squamous cell carcinoma non-small cell lung cancer esophageal cancer immunotherapy guidance tumor biomarker imaging